Many diseases of the aging population-atherosclerosis, hypertension, pulmonary fibrosis, and a variety of ocular pathologies-have their roots in the loss of control over key metabolic and physiological processes in earlier stages of life. IN order to establish a systematic approach to dissect the functions of these and other orphan nuclear receptors, LXR and FXR will be studied in a systematic fashion by guidelines developed by the Receptor Atlas Group (RAG). This includes construction of a standardized mouse tissue RNA array for quantitative PCR analysis. In this manner, receptor expression patterns, as well as target genes identified by a universal microarray platform, will be collected to build a relational database of nuclear receptor metabolic function. Additionally,, the RAG will utilize a consistent, methodology to analyze the function of orphan nuclear receptors in response to dietary manipulations, pharmacologic treatments, and diurnal variations in gene expression in both wild type and transgenic knock-in mouse lines. The data collected in this manner will be contained within a shared Bioinformatics Resource where RAG and other laboratories can compare ONR function on a common scientific platform.